Content area
Abstract
To investigate whether the Pediatric Regulation has already succeeded in addressing the needs of the pediatric population both quantitatively with respect to pediatric development plans and trials, and qualitatively with respect to the content of the plans. The Pediatric Regulation No 1901/2006 entered into force in Europe on 26 January 2007, with the aim to improve the development of medicinal products, to address the lack of age-appropriate formulations and to provide information on efficacy, safety and dosing for the pediatric population. The Regulation requires applications for marketing authorizations to be accompanied by either a product-specific waiver or a pediatric investigation plan, to be agreed by the Pediatric Committee (PDCO) of the European Medicines Agency (EMA). A retrospective analysis of the applications for Pediatric Investigation Plans (PIPs) and Waivers submitted to the EMA, from 2007 until end of 2009, was performed. The content of scientific opinions adopted by the Pediatric Committee was compared to the proposals submitted by industry, and the pediatric clinical trials registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database were examined. An increasing pediatric medicine development can be expected following the adoption of this legal framework. The highest number of PIPs was in the fields of endocrinology (13.4%), oncology (11%) and infectious (10.8%) and cardiovascular diseases (7.1%), but most therapeutic areas now benefit from pediatric development. A large number of PIPs include measures for the development of age-appropriate formulations (23%), and most include studies on dosing, efficacy and safety to cover the respective pediatric subsets, including the mostly neglected neonates (26%). In many proposals (38%), however, the PDCO had to request major modifications to the proposed PIPs to ensure that the results will meet the needs, in particular by requesting better methodology. The proportion of pediatric trials as a percentage of all clinical trials has moderately increased (from 8.2 to 9.4% of all trials), and this may reflect the fact that pediatric trials are generally deferred (82%) until after adult development. This is the first analysis of the general impact of the Pediatric Regulation on the development of medicinal products in Europe. Three years after the implementation of the Pediatric Regulation, we were able to identify that the PIPs address the main gaps in knowledge on pediatric medicines. The key objective of the Pediatric Regulation, namely, the availability of medicines with age-appropriate information, is going to be achieved. It is clear also that modifications of the initial proposals as requested by the PDCO are necessary to ensure the quality of pediatric developments. The impact on the number of clinical trials performed remains modest at this point in time, and it will be of high interest to monitor this performance indicator, which will also inform us whether pediatric medicine research takes place in Europe or elsewhere. [PUBLICATION ABSTRACT]